PROJECT ABSTRACT This project, entitled ?Treatment with Lorcaserin for Cocaine use: The TLC Study,? will evaluate the impact of a pharmacologic intervention among men who have sex with men (MSM) with cocaine use disorders. It is in response to PA-15-177, which supports pilot and feasibility studies for substance use interventions, in preparation for full-scale trials. Cocaine use is an unrelenting public health problem that is associated with serious morbidity and mortality. In both powder and rock (i.e., ?crack?) form, cocaine is an addictive psychostimulant; it is estimated that up to one in six cocaine users may develop dependence. Cocaine is the leading cause of illicit substance-related emergency department visits in the US and it is associated with direct cardiac toxicity, myocardial infarctions and sudden cardiac death. Among men who have sex with men (MSM), cocaine use is a major public health issue. Cocaine use among MSM is estimated to be 15 times more prevalent compared to the general population. In San Francisco, cocaine use has significantly increased among MSM, from 19% in 2005 to 35% in 2014. Despite the high prevalence of cocaine use among MSM, few interventions have been proven to be effective in reducing cocaine use in this population. There are no FDA-approved medications for cocaine use disorders, which severely limits treatment options. Lorcaserin, a novel selective serotonin (5-HT) receptor agonist, may be a promising agent to treat cocaine use disorders. Preclinical studies have shown that lorcaserin has been associated with cocaine self-administration in non-human primates. We postulate that lorcaserin's dual effects of inhibiting dopamine levels and decreasing impulsivity may effectively help MSM reduce or stop their cocaine use. However, there have been no studies that have evaluated the feasibility, tolerability, acceptability, adherence and preliminary efficacy of lorcaserin among actively using MSM with cocaine use disorders. Research Design: This is a pilot randomized, double-blind, placebo-controlled 12-week trial that will evaluate the feasibility, tolerability, acceptability, adherence and preliminary efficacy of lorcaserin among 45 MSM with cocaine use disorders. Participants will be randomly assigned (2:1) to receive 12 weeks of lorcaserin 10mg (n=30) or placebo (n=15), to be taken twice a day. The Structured Clinical Interview for the DSM-V (SCID) will be used to screen for cocaine use disorders. After enrollment, participants will be seen weekly to receive study drug and substance use counseling, and twice weekly for urine collection. Safety laboratory assessments, vital signs, and computer assisted personal interviews (CAPI) will be completed monthly. Feasibility, tolerability, and acceptability and adherence (Aims 1-3) will be assessed upon trial completion using enrollment and retention rates, frequency of adverse clinical events, participant evaluation and study process outcomes and adherence from WisePill Dispenser data at week 12. Cocaine use will be assessed via twice weekly urinalysis (Aim 4). HIV-related sexual risk behaviors will be assess via CAPI (Aim 4).